OPIOID Rx & Safety

OPIOID Rx & Safety [General]
This section focuses on dispelling the myths surrounding opioid agonists. Clinical guidance is provided for more effective application and prescribing of these vital pain medications, with a special emphasis on safety and risk management issues to prevent misuse and adverse events.

NOTE: All URL links listed below were valid at the time of posting; however, the Internet is constantly changing and some linked sites may move or become inactive with time. Please notify us of any broken links at: [email protected]


 Also of interest, Opioid Therapy & Safety Guidelines <Click Here>

Also see the following articles in the Current Comments section…


PCSS-O (Prescribers’ Clinical Support System for Opioid Therapies)

From: CSAT/SAMHSA and multi-organizational collaboration; 2012-ongoing.

Access PCSS-O website at: http://www.pcss-o.org/

This multi-organizational collaboration is sponsored by the U.S. Center for Substance Abuse Treatment/Substance Abuse and Mental Health Services Administration (CSAT/SAMHSA). The website offers online and webinar-based training in the safe and effective treatment of patients receiving opioid medications, either for the treatment of pain or for the treatment of opioid dependence. Additionally, this program offers a Peer Support Program in which prescribers can get questions answered by experts in the field regarding the safe use of opioid medications. Accessed 5/10/12.

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Online Opioid Conversion Calculator

From: Practical Pain Management journal; 2012.

Access calculator here: http://opioidcalculator.practicalpainmanagement.com/

See article discussing the calculator here: http://pain-topics.org/pdf/PPM-Opioid-Calculator-2012.pdf

This free, online resource is probably the most current, comprehensive, and accurate tool of its type for calculating appropriate opioid doses for either opioid-naïve patients or when switching from one agent to another, including the more difficult calculations for methadone conversions. It was developed by 3 experts in the field — Michael J. Brennan, MD, MS; Jeffrey Fudin, BS, PharmD, FCCP; and Ruth J. Perkins, BS, MA, PharmD, BCPS — who placed a special emphasis on the latest medical evidence and safety in arriving at their recommendations. So, by having this online tool, clinicians can — with the patient in the room — do helpful dosing calculations for starting opioid therapy or switching patients from one medication to another using an easy, science-based, state-of-the-art approach. Access checked 5/4/12.

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Management of Drug-Drug Interactions: Considerations for Special Populations — Focus on Opioid Use in the Elderly and Long Term Care

By: Tom Lynch, PharmD, BCPS. American Journal of Managed Care. 2011;17(Suppl 11):S293-S298 (6 pp).

See full-text article at: http://www.ajmc.com/publications/…/A370_11sep_Opioid_S293-S298/

Prescribing opioids to elderly patients and long-term care residents can be challenging because physiological changes can affect opioid pharmacokinetics. Opioid therapy in these 2 populations has not been well studied and many factors — including communication problems, comorbidities, and inconsistent medication therapy adherence — can affect drug-drug interactions. The potential for elderly patients to experience physiological changes in their cytochrome P450 enzyme system can affect certain drugs or drug combinations and cause adverse effects or therapeutic failures. Discussions include a review of specific factors, like cardiovascular changes and a decline in renal functional, which can alter a patient’s circulating opioid concentration. A table containing a list of questions to help clinicians identify a patient’s potential for drug-drug interactions is included. Recommendations also are made for pain management in elderly and younger patients in long term care who may be taking multiple medications. Access checked 2/16/12.

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Pharmacology of Opioids in the Treatment of Chronic Pain Syndromes

By: Ricardo Vallejo, MD, PhD; Robert L. Barkin, PharmD; Victor C. Wang, PhD. Pain Physician; 2011;14(4):E343-E360 (18pp).

PDF available at: http://www.painphysicianjournal.com/2011/july/2011;14;E343-E360.pdf

The authors remind practitioners of the need for knowledge and vigilance when prescribing opioids for patients with chronic noncancer. A brief review of the 4 chemical classes of opioids — agonists, agonist-antagonists, partial agonists, and antagonists — includes a discussion of opioid potency, variations in receptor site binding affinities, and the importance of opioid concentration at the receptor site. Information provided for 14 specific opioid analgesics includes an explanation of the drug disposition kinetics and actions for each agent, as well as helpful administration facts like typical dosing considerations and common adverse effects. Access checked 1/06/12.

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Management of Opioid Tolerability and Related Adverse Effects

By: Dmitry Arbuck, MD, Christopher Gharibo, MD, Sumedha Labhsetwar, MD, et al. J Med. 2010;3(1):1-10 (10pp).

PDF available at: http://pain-topics.org/pdf/ArbuckEtal-2010.pdf

Opioid analgesics are effective but are not always well tolerated by patients. Adverse effects of opioids may be classed as inhibitory or excitatory, although they sometimes occur simultaneously. These can be treatment limiting; however, a number of counter strategies exist and are discussed in this excellent review, including: opioid rotation and/or alternate analgesics, the selective use of opioid antagonists, and adjunctive therapies to reduce adverse effects. Using different approaches, taking intra-patient variability into account, adverse opioid effects can be effectively managed for better patient care. Access checked 1/10/2012.

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Managing Chronic Pain with Opioids: A Call for Change

By: Paul Arnstein, PhD, RN; Barbara St. Marie, ANP. Nurse Practitioner Healthcare Foundation. Dec 15, 2010.

PDF available at: http://www.nphealthcarefoundation.org/programs/downloads/white_paper_opioids.pdf

This white paper from the Nurse Practitioner Healthcare Foundation begins with a reminder of the rising number of persons with inadequately managed pain and discusses key barriers to the treatment of chronic pain with opioids. Recommendations are made for enhancing practitioner education on all topics related to opioid prescribing and the management of chronic pain. Challenges and recommendations related to the need for the allocation of additional professional time for patient education and counseling are explored. An important resource noted for patient education is Opioids911-Safety. Additionally, the authors encourage practitioners to be familiar with pain policies, including those related to reimbursement and drug availability. Access checked 1/05/11.

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Help for Safely Using Opioid Pain Relievers from Pain Treatment Topics

See website at: http://Opioids911.org

Opioids911-Safety is an independent, noncommercial, Internet-based educational activity from Pain Treatment Topics for patients and their family caregivers focusing on the proper and safe use of opioid pain relievers. The mission is to provide an understanding of opioid analgesics and their various risks, and to suggest specific actions for preventing opioid-related problems, including: misuse, abuse, addiction, diversion, adverse reactions, overmedication, and life-threatening overdose. Instruction is provided on recognizing opioid problems if they do occur and on being prepared for what to do during an emergency. Guidance is provided for healthcare providers in using the program at the point-of-care. Access checked 10/15/10.

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Patients Who Require Ultra-High Opioid Doses

By: Schneider J, Anderson A, Tennant F. Patients who require ultra-high opioid doses. PPM. 2009(Sep);9(7):10+.


PDF available at: http://pain-topics.org/pdf/PPM_Sept09_UltraHighOpioid.pdf

Controversy still exists about the long-term prescribing of opioids for chronic noncancer pain (CNCP) conditions, and particularly regarding the safety and effectiveness of higher opioid doses. Yet, there appears to be a subset of patients with CNCP who require and thrive on ultra-high morphine-equivalent opioid doses exceeding 1,000 mg/day — demonstrating that what some practitioners might consider as being way too much opioid is just the right amount for certain patients. Full article download courtesy of Practical Pain Management. For more information on this journal [click here]. Access checked 9/25/09.

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Opioid Metabolism

By: Howard S. Smith, MD. Mayo Clin. Proc. 2009(Jul);84(7):613-624.

See document at: http://www.mayoclinicproceedings.com/content/84/7/613.full

This excellent review, of interest for all healthcare providers, describes the basics of opioid analgesic metabolism and the factors influencing it. Recommendations are provided for addressing metabolic issues that may compromise effective pain management. Of critical importance, individual patients differ in their response to specific opioid analgesics and they may require trials of several opioids before finding an agent that provides effective analgesia with acceptable tolerability. Access checked 7/24/09.

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A Comparison of Long- and Short-Acting Opioids for the Treatment of Chronic Noncancer Pain: Tailoring Therapy to Meet Patient Needs

By: Charles E. Argoff, MD and Daniel I. Silvershein, MD. Mayo Clin. Proc. 2009(Jul);84(7):602-612.

See document at: http://www.mayoclinicproceedings.com/content/84/7/602.full

When considering opioid analgesics for the management of chronic noncancer pain (CNCP) prescribers need to understand the pharmacokinetics and pharmacodynamics of the various opioid formulations as they relate to the temporal characteristics of the patient’s pain. This article aids in deciding whether to prescribe a short-acting opioid with a relatively quick onset of action and short duration of analgesic activity, a long-acting opioid with a longer duration of analgesic action but a potentially longer onset of action, or both. Studies suggest that both types of opioids are effective for most CNCP conditions; however, opioid therapy should be tailored to the pain state and the individual patient. Access checked 7/24/09.

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Opioid Pharmacology

By: Andrea M. Trescot, MD, et al. Pain Physician; 2008(March);11:S133-S153 (26pp).

PDF available at: http://www.painphysicianjournal.com/2008/april/2008;11;S133-S153.pdf

This document provides an excellent clinical overview of opioid history, structure, receptors, and pharmacokinetics. A number of opioid analgesics available for clinical use are covered, including morphine, codeine, hydrocodone, hydromorphone, oxycodone, fentanyl, methadone, meperidine, propoxyphene, buprenorphine, levorphanol, and tramadol. The 4 chemical classes of opioids are described. Distinctions are made between opioid agonists, partial agonists, agonist-antagonists, as well as pure antagonists.

The authors examine the structure, chemistry, and metabolism of opioids to help healthcare providers better understand the side effects, drug interactions, and individual responses of patients receiving opioids. Advantages and disadvantages of the various opioids in the management of pain are discussed. Many helpful tables and charts are included. Access checked 6/15/09.

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Opioid Safety in Patients With Renal or Hepatic Dysfunction
By: Sarah J. Johnson, PharmD; from Pain Treatment Topics, Updated November 30, 2007.

PDF available here for download: Opioids-Renal-Hepatic-Dysfunction.pdf (225 KB, 9 pp)

Patients with kidney or liver disorders often need opioid analgesics for effective pain relief. However, there is a risk of opioid overdose or other adverse events in these patients due to the possibility of altered drug pharmacokinetics and toxic accumulation of the parent opioid and/or its metabolites. This evidence-based report exclusively from Pain Treatment Topics provides a comprehensive list of clinical cautions and dosing recommendations relating to various opioids.

Prescribing Pointers in the Report: In renal or hepatic dysfunction, usual or adjusted doses may be appropriate for certain opioids, including morphine, hydromorphone, hydrocodone. Other opioids should be avoided at all times – including codeine, meperidine, and propoxyphene – and oxycodone should not be used in dialysis patients. Methadone and fentanyl are generally not first-line therapies, although they can be carefully used in patients with renal dysfunction or on dialysis, but methadone is not advised in severe liver failure. For most patients with kidney or liver disease, either morphine or hydromorphone could be a good starting therapy if an opioid agent is appropriate for pain relief.

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Opioid Analgesics for Chronic Pain

By: Mary Lou Bossio, NP; from Advance for Physician Assistants; 2007.

HTML online at: http://physician-assistant.advanceweb.com/Common/editorial/editorial.aspx?CC=84278

An appreciation of chronic pain and its prevalence, along with a thorough understanding of provider responsibilities, patient rights, and the appropriateness of opioid analgesics for this population are needed. Such knowledge provides a foundation for evaluating chronic pain and developing an individualized management plan.

In this brief paper, the author emphasizes that, when opioids are used, prepare for both expected and unexpected results. The goal for clinicians in all settings is to responsibly offer opioid analgesic therapy to patients for whom it is indicated and justified. Additionally, healthcare providers must ensure that opioids are not being used for nonmedical reasons. The authors note, “We can try to minimize the risk of deception and provide pain relief for some, or we can accept the risk and ensure pain relief for all.”

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Managing Opioid-Induced Constipation in Ambulatory-Care Patients

By: Clyde R. Goodheart, MD, MBA, MS; Stewart B. Leavitt, MA, PhD; from Pain Treatment Topics, August 2006.

PDF available here for download: Managing_Opioid-Induced_Constipation.pdf (180 KB; 9 pp)

Opioid-Induced_ConstipationConstipation is a frequent side effect of opioid therapy since these agents decrease peristaltic activity in the gastrointestinal tract. Because of the mechanisms involved in opioid-induced constipation, some treatments that may be applicable for common, functional constipation are inappropriate for ambulatory-care patients prescribed opioid analgesics.

The distress of constipation in these patients may add to the discomfort already present from pain, and they might decrease or discontinue opioid therapy to avoid constipation. So, motivating such patients to comply with their opioid regimen also requires a special approach for managing constipation.

Certain popular beliefs about treating constipation have little or no evidence to support them. For example, adding fluids or fiber to the diet, and increasing activity, may be unhelpful in patients with opioid-induced constipation. In most cases, laxative therapy will be needed for prevention or for treatment of existing constipation.

Also see: Constipation… from Consumer Reports Best Buy Drugs, December 2008.


This document discusses the various causes of constipation and the full range of treatment options, including their costs. For constipation triggered by an opioid drug, over-the-counter polyethylene glycol is recommended by Consumer Reports as effective and economical laxative therapy.

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Overview of Oral Modified-Release Opioid Products for the Management of Chronic Pain

By: Calene M. Amabile, PharmD, BCPS, and Bill J. Bowman, BSPharm, PhD. Medscape, Ann Pharmacother; 2006;40(7).

Available online at: http://www.medscape.com/viewarticle/542574

Oral modified-release opioid products have enabled patients to better maintain pain control via convenient dosing intervals and sustained blood concentrations, which also may decrease side effects. The differences between available oral modified-release products involve their half-life, cost, and formulation. Modified-release delivery systems incorporate what has been termed extended-release (ER), controlled-release (CR), or sustained-release (SR) mechanisms. While specific definitions of these are sometimes non-specific, there are differences in modified-release technologies that can impact patient response to individual products. This paper describes those differences and provides useful information for product selection. Accessed 2/5/08.

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Opioid Tapering: Safely Discontinuing Opioid Analgesics

By: Lee A. Kral, PharmD, BCPS; from Pain Treatment Topics, March 2006.

PDF available here for download: Safely_Tapering_Opioids.pdf (140 KB; 7 pp)

There are many reasons for considering opioid analgesic tapering, both from healthcare-provider and patient perspectives. Whereas, guidance for starting opioid analgesics can be obtained from product package inserts and reference sources, it is much more difficult to find reliable information about switching or stopping these medications. Some practitioners have their own protocols for managing conversions or tapers; although, there is no single strategy that can be applied to all patients and each situation must be handled on an individual basis

This paper discusses the many factors to consider when discontinuing opioid analgesics, and it presents specific and practical clinical guidance for establishing protocols that maximize patient safety and comfort during the process. Important advice for patients regarding emergency tapering – such as following natural disasters or other crises when medication is inaccessible – also is provided.

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Opioids for Chronic Nonterminal Pain

By: Jane C. Ballantyne, MD, FRCA; from Medscape; South Med J, 99(11); 2006.

HTML article available online at: http://www.medscape.com/viewarticle/549294

This article reviews the evidence for and against chronic opioid therapy. Concerns have arisen about loss of efficacy with prolonged use, possibly related to tolerance or opioid-induced hyperalgesia, and these mechanisms are discussed. It is clear from current evidence that many patients abandon chronic opioid therapy because of the unacceptability of side effects. There are also concerns about toxicity, especially when opioids are used in high doses for prolonged periods, related to hormonal and immune function.

The issue of addiction during opioid treatment of chronic pain is also explored. Opioid treatment of pain has been, and remains, severely hampered because of actual and legal constraints related to addiction risk. A structured goal-directed approach to chronic opioid treatment is suggested, which aims to select and monitor patients carefully, and wean therapy if treatment goals are not reached.

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VA/DoD Clinical Practice Guideline for the Management of Opioid Therapy for Chronic Pain

From: Department of Veterans Affairs, Department of Defense; 2003.

PDF available here for download: VA_OpioidsChronicPain_Guide.pdf (1.82 MB, 111 pp)

For updated versions of this same Guideline click HERE.

Citing the high prevalence and inadequate treatment of chronic pain, the U.S. Department of Veterans Affairs (VA) identified pain management as a priority. In partnership with the Department of Defense (DoD), a panel of experts used an evidence-based approach focusing on chronic opioid therapy (lasting for more than one month). Comprehensively, the guideline addresses pain assessment, therapy indications and contraindications, and patient education. Recommendations and algorithms for all 3 phases of opioid management are presented: 1) initiation phase, 2) titration, and 3) maintenance. Assessments of efficacy, nonadherence, adverse effects, and followup are explored.

As a companion to this document, also see…

Opioid Assessment & Treatment Pocket Guide

PDF available here for download: VA_OpioidPocket_Guide.pdf (233 KB, 2 pp)

Opioid Medications [Dosing] Pocket Guide

PDF available here for download: VA_OpioidDosing_Guide.pdf (169 KB, 2 pp)

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Opioid/Medication Safety Information for Your Patients….

These Patient Resources are for the benefit of healthcare providers to make available for their patients, as appropriate. They have been reviewed by Pain Treatment Topics staff; however, professional discretion in their distribution and application is advised.

Special documents address the following vital topics…See details…>

  • Proper & Safe Disposal of Prescription Drugs
  • Facts About Safely Using Opioids in General
  • Guidance on Safely Using Methadone or Oxycodone
  • Facts About Prescription Drug Abuse
  • Buying Prescription Medicine Online: A Consumer Safety Guide

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